The objective of this fellowship application is to determine the gene expression profile in berberine-treated human cancer cells. An increasing amount of attention has been paid to the use of complementary and alternative medicine (CAM) as a part of the treatment for human cancer. A Chinese herb, Coptis chinensis, that is routinely used in China for treating gastroenteritis for thousands of years, may be developed as an anti-tumor agent. Coptis contains multiple constituents, and berberine is the major constituent. We have recently demonstrated that Coptis extract and berberine exhibit significant anti-proliferative activity in human cancer cells. However, the molecular mechanisms underlying Coptis or berberine-mediated anti-tumor activity are unknown. In this application, I propose to conduct a comprehensive gene expression profiling analysis in berberine-treated human cancer cells by focusing on three specific aims. The first aim is to conduct hybridizations of RNA samples prepared from berberine-treated human cancer cells. The second aim is to conduct comprehensive bioinformatic analyses on the microarray data set. The third aim is to verify potentially important targets of berberine using Northern blotting or quantitative RT-PCR. Taken together, by analyzing the expression profile of nearly 40,000 genes, I expect to identify a set of target genes that may function as intracellular mediators of berberine's anti-cancer action. My long-term goal is to elucidate the molecular bases of berberine-mediated antitumor activity, and to investigate the possible use of berberine and its derivatives as effective chemotherapy and/or chemopreventive agents in human cancer.